This review evaluates the current understanding of the benefits and risks of physical activity and exercise on the gastrointestinal system. A significant portion of endurance athletes are affected by gastrointestinal symptoms, but most symptoms are transient and do not have long-term consequences. Conversely, physical activity may have a protective effect on the gastrointestinal system. There is convincing evidence that physical activity reduces the risk of colon cancer. The evidence is less convincing for gastric and pancreatic cancers, gastroesophageal reflux disease, peptic ulcer disease, nonalcoholic fatty liver disease, cholelithiasis, diverticular disease, irritable bowel syndrome, and constipation. Physical activity may reduce the risk of gastrointestinal bleeding and inflammatory bowel disease, although this has not been proven unequivocally. This article provides a critical review of the evidence-based literature concerning exercise and physical activity effects on the gastrointestinal system and provides physicians with a better understanding of the evidence behind exercise prescriptions for patients with gastrointestinal disorders. Well-designed prospective randomized trials evaluating the risks and benefits of exercise and physical activity on gastrointestinal disorders are recommended for future research.